Aims: This study is part of an ongoing investigation into the mechanisms responsible for man's ventilatory acclimatization to chronic hypoxemia. Specifically, the proposed study will examine the role of CSF (H plus) regulation and chemoreceptor stimulation in this process by testing the dependence of CSF (HCO3) and CSF (H plus) regulation on changes in plasma (HCO3) during sustained hypocapnia and/or hypoxemia of varying severity. Design: To quantitate the dependence of CSF (HCO3) regulation on plasma (HCO3), hypoxemia, hypercapnia and varying combinations of same, will be imposed for 9 to 18 hours in anesthetized, paralyzed dogs; and the independent variable--(HCO3)--will be either: a) permitted to change via the usual buffering and compensatory mechanisms; or b) maintained by carefully monitored NaHCO3 (iv) at or within 1 to 2 meg/1 above control values. In essence, then, the proposed study attempts an experimental testing and quantitation of the similarity between blood and CSF in (H plus) regulation that we have previously observed in man and pony in chronic hypoxia and/or hypocapnia (PaO2 39 to 55, PaCO2 25-32mmHg). In addition some "severe" conditions of hypocapnia (less than 20 PaCO2) and hypoxia (30-35 PaO2) are included in the present study to quantitate the contribution of "CSF specific" mechanisms to the regulation of CSF (HCO3). It is postulated that, unlike chronic metabolic acid-base derangement or respiratory acidosis, ventilatory acclimatization to chronic hypocapnia and/or hypoxemia--at least in these conditions within the "patho-physiologic" range--is not meditated by medullary (H plus) stimulation.